Neonatal bacterial sepsis has continued in this decade to contribute significantly to neonatal mortality and morbidity and is a critical determinant of outcome in infants of very low birth weight despite the availability of antibiotics. The group B Streptococcus and Escherichia coli are the predominant pathogens for the newborn infant. Studies on the epidemiology, microbiology, and immunology of group B streptococcal disease are more extensive than those on E. coli disease. Type-specific antibodies, polymorphonuclear leukocytes, and complement are integral to immunity against group B Streptococcus, and experimental data are presented to support the importance of these components. The newborn infant is handicapped by temporary deficiencies in host defenses, and approaches for restoring immunocompetence, such as immunization of the mother or passive administration of intravenous immunoglobulins or other immune factors, are presented for consideration. Further studies are required to demonstrate the safety, feasibility, and efficacy of these approaches.